Studies on temperate bacteriophage Mu have contributed to several concepts in molecular genetics. Mu has provided insights into the mechanisms of DNA transposition. DNA transpositions and their attendant DNA rearrangements are important genetic phenomena. They have been invoked to explain rapid evolution and speciation, and have been implicated in some aspects of differentiation amd cellular transformation. Continuous excitement in this field is exemplified by the recent suggestions that DNA rearrangements might constitute a general mechanism for tumor induction, possibly by their effects on cellular oncogens. Mu is a virus as well as transposon and this combination is reflected in its life style. Like any other virus, it replicates its DNA efficiently, making many copies of itself within a short span of time. Like any other transposable element, it can move its DNA by a transposition process involving DNA replication. Mu DNA can also be excised from host DNA. This process is remarkable because it is catalyzed by the A gene product, the transposase of Mu. The transposase must recognize both ends for excision and yet the two ends of Mu are not symmetrical with respect to their nucleotide sequences. We propose to further disssect the processes of Mu transposition and excision by genetic, biochemical and electron microscopic techniques. We will find out exactly which sequences at the ends of Mu are required for excision and transposition. We will define, at the nucleotide sequence level, Mu-promoted excision events and will study the different parameters which affect excision. We will develop in vitro assays for transposition and excision. As a corrollary to this work, the Mu A protein (the transposasae) and the B protein ( the transposition amplifier) will be purified from overproducing strains. To understand the mechanism of the flip-flop of the G segment of Mu, we will purify the gin protein and use plasmid substrates constructed in vitro to study inversion in vivo as well as in vitro.